1. Field of the Invention
The invention pertains to methods for treating certain diseases and disorders associated with inflammatory and immunoregulatory responses. More particularly, the present invention involves treating rheumatoid arthritis by administering an IL-17 inhibitor or IL-17 antagonist, in particular IL-17 receptor, to an individual afflicted with such rheumatoid arthritis.
2. Description of Related Art
Cytokines are hormone-like molecules that regulate various aspects of an immune or inflammatory response. Cytokines exert their effects by specifically binding receptors present on cells, and transducing a signal to the cells. Rouvier et al. (J. Immunol. 150:5445; 1993) reported a novel cDNA which they termed CTLA-8; cloning of the human homolog led to the identification of this family of molecules as Interleukin-17 (IL-17; Yao et al., Immunity 3:811; 1995). IL-17 is a cytokine produced by activated T cells that stimulates the secretion of various proinflammatory molecules, including tumor necrosis factor xcex1 (TNF-xcex1), Interleukin-1 xcex2 (IL-1xcex2) and prostaglandin E2 (PGE2) from macrophages (Jovanovic et al., J. Immunol. 160:3513; 1998).
TNF-xcex1 and IL-1 are believed to play a role in the inflammation and bone destruction that occurs in rheumatoid arthritis (RA), albeit through different mechanisms (Joosten et al., J. Immunol. 163:5049; 1999). Moreover, elevated levels of IL-17 have been reported to occur in the synovial fluid of RA patients, and may play a role in the bone destruction characteristic of RA (Chabaud et al., Arthritis Rheum. 42:963, 1999; Jovanovic et al., Arthritis Rheum. 43:1134, 2000).
IL-17 acts on cells by binding to a specific receptor, IL-17R, which was isolated as described U.S. Pat. No. 6,072,033, issued Jun. 6, 2000. IL-17R is present on numerous cell types, including synoviocytes and monocytes/macrophages. Although there are numerous agents known in the art that are used in the treatment of RA, there is a need to identify additional molecules that can be used to treat or ameliorate the symptoms of this chronic inflammatory disease.
The present invention relates to a method of treating a mammal afflicted with a condition that relates to an inflammatory response, in particular, rheumatoid arthritis, by administering an IL-17 antagonist that inhibits IL-17 mediated signaling to a cell via membrane-bound IL-17 receptor. Suitable IL-17 antagonists include soluble IL-17 receptor, antagonistic antibodies that specifically bind IL-17, antagonistic antibodies to IL-17 receptor and combinations thereof.
Provided herein are methods for treating medical disorders associated with IL-17 mediated inflammatory reactions or IL-17 mediated immunoregulatory reactions. The methods of the present invention include administering an IL-17 antagonist, or IL-1 inhibitor, that inhibits IL-17 inflammatory or immunoregulatory signaling, to an individual afflicted with an inflammatory or immunoregulatory disease mediated by IL-17. More particularly, the present invention involves administering an IL-17 antagonist such as IL-17 receptor, to an individual inflicted with rheumatoid arthritis, for a period of time sufficient to induce a sustained improvement in the patient""s condition.